tbuckley/cabot-search huggingface dataset:
POS0097 ASSOCIATION BETWEEN LOSS OF IMMUNE CHECKPOINT PROGRAMMED CELL DEATH PROTEIN 1 AND ACTIVE ANCA-ASSOCIATED RENAL VASCULITIS
Authors: B. Tampe
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Immune checkpoint inhibitors (ICIs) have made an important contribution on the survival of patients with certain cancers. ICIs interrupt co-inhibitory signalling pathways mediated by programmed cell death protein 1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen (CTLA-4) that result in the elimination of cancer cells by stimulating the immune system. <h3>Objectives</h3> Immune-related adverse events have also been described and attributed to an enhanced immune system activation. Recent observations have suggested dysregulation of immune checkpoints in active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Therefore, we here aimed to analyze abundance of immune checkpoint molecules PD-1/PD-L1 and its implications in ANCA-associated renal vasculitis. <h3>Methods</h3> We here analyzed intrarenal PD-1 and PD-L1 by immunostaining in a total number of 15 kidney biopsies with ANCA-associated renal vasculitis in correlation with glomerular and tubulointer-stitial lesions. For independent validation, publicly available datasets were analyzed for PD-1 expression (encoded by PDCD1). <h3>Results</h3> We here observed a predominant tubulointerstitial expression of PD-1 that is decreased in ANCA-associated renal vasculitis. Moreover, loss of tubulointerstitial PD-1 correlated with active ANCA-associated renal vasculitis. Consistent to the observed association with active glomerular and tubulointerstitial lesions, we identified that interstitial PD-1 correlated with tubular and/or glomerular PD-L1 positivity. Finally, PD-1 was associated with decreased local synthesis of complement factor B. Interestingly, we did not observe a correlation between PD-1 and complement C5 or its C5a receptor. Combined with our observations, this may implicate a link between im-paired PD-1/PD-L1 signalling, complement factor B, and active ANCA-associated renal vasculitis. <h3>Conclusion</h3> These findings could be of relevance because experimental data have already been described that PD-1 agonism can be used therapeutically to attenuate autoimmunity in multiple disease models. Furthermore, targeted therapy against complement C5/C5a receptor and factor B are both available and currently evolving in the treatment of AAV. Therefore, this pilot study expands our current knowledge and describes a potential interplay between immune checkpoints and the alternative complement pathway in active ANCA-associated renal vasculitis. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Björn Tampe Grant/research support from: Support from Evotec and Vifor.
POS0101 FRAILTY CHANGES FOLLOWING TOTAL KNEE ARTHROPLASTY ARE ASSOCIATED WITH FUNCTIONAL IMPROVEMENT RATHER THAN PAIN RELIEF IN THE PATIENTS WITH END-STAGE KNEE ARTHROSIS
Authors: K. Inui, S. Maeda, S. Yamada, K. Mandai, T. Hashimura, T. Tachibana, H. Ohashi, T. Ikawa
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Knee joint disorders in the elderly result in physical frailty and limiting healthy living. Although total knee arthroplasty (TKA) achieves significant pain relief and functional improvement, the effect of TKA on Frailty is not clear. <h3>Objectives</h3> This study aimed to investigate the change in frailty at 1 year postoperatively in patients undergoing primary TKA and to examine the correlated factors with this frailty change. <h3>Methods</h3> Patients with end-stage knee arthrosis who underwent primary TKA at our hospital between July 2020 and May 2021 were included with written consent. Basic attributes such as age, gender and BMI, with appendicular skeletal muscle mass (ASMI) by whole-body mode DXA, presence of sarcopenia by Asian Working Group for Sarcopenia 2019 criteria were measured preoperatively, and VAS for pain during walking, clinical assessment of knee joint function (Knee Society Score: KSS), quadriceps muscle strength by dynamometer, range of motion (ROM), and walking speed were measured before and one year after surgery. The relationship between the changes in the degree of frailty (Japanese Cardiovascular Health Study criteria for frailty) before and 1 year postoperatively. <h3>Results</h3> Seventy-five patients (59 women, mean age 75 years) were included in the study. In univariate analysis, KSS, ROM, muscle strength, and VAS for pain were significantly improved at 1 year after TKA compared to preoperative values (p&lt;0.0001, 0.0001, 0.0001, 0.0001: pared <i>t</i>-test). The number of frail patients was decreased from 24 to 18 following TKA (p=0.002: Fisher's exact test). Multivariate analysis of the association of changes in frailty using ordinal logistic regression showed a positive correlation between improvement in walking speed and improvement in muscle strength (p=0.01, p=0.02), but not with sex, age, preoperative ASMI or presence of sarcopenia, improvement in pain while walking or ROM (Table 1). <h3>Conclusion</h3> The number of patients with frailty significantly decreased 1 year after TKA; the factors associated with changes in frailty were improvements in gait speed and muscle strength, suggesting that functional improvement rather than the pain-relieving effects of TKA contributed to the improvement in frail. <h3>Acknowledgements</h3> We are grateful to Toshiko Yokoi, Mayu Hashizume, Madoka Sakai, Mayu Ikemizu for the data collection. We also wish to thank all the PT staffs in our hospital who participated in this study. <h3>Disclosure of Interests</h3> None Declared.
POS0161 AN ULTRASOUND SCORING SYSTEM BASED ON THE SIZE AND NUMBER OF EROSIONS IS RELIABLE IN RHEUMATOID ARTHRITIS
Authors: P. Mandl, I. Gessl, G. Filippou, S. Sirotti, L. Terslev, C. Pineda, E. Cipolletta, P. Collado, C. Dejaco, A. Delle Sedie, C. Duftner, H. B. Hammer, A. Iagnocco, I. Möller, E. Naredo, M. Szkudlarek, G. Tamborrini, R. Wakefield, P. Wong, E. Filippucci, P. Balint, M. A. D’agostino
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ultrasound has been shown to be a valid tool for the evaluation of bone erosions in rheumatoid arthritis (RA), yet a consensual scoring system is lacking. <h3>Objectives</h3> To assess the reliability of a semiquantitative scoring system for assessing structural bone erosion by ultrasound in a web-based reliability exercise. <h3>Methods</h3> A task force of the OMERACT Ultrasound Working Group developed definitions and a scoring system for grading bone erosions which takes both the size and number of erosions into consideration. Pairs of static images (longitudinal and transverse) in DICOM format of metacarpophalangeal and proximal interphalangeal joints 2-5 were acquired prospectively in healthy controls and in RA patients with varying degrees of pathology by the task force members. A dataset of anonymized images, representing various grades was created and utilized in a web-based exercise using the cmrad.com cloud platform which allowed the participants to measure the size of the erosions and use the discrete measures and the number of erosions to grade each joint according to the scoring system. Both the longitudinal and transverse scans were considered and the largest diameter chosen for each erosion. Intra- and inter-reader reliability of the scoring system was assessed using kappa statistics. <h3>Results</h3> A 4-grade semiquantitative scoring system was developed: grade 0) intact cortical bone; grade 1) single small erosion (diameter: ≤2mm); grade 2) single large erosion (diameter: &gt;2mm) or 2 small erosions or 1 large and 1 small erosion; grade 3) 2 large erosions or ≥3 erosions, regardless of size (Figure 1). A dataset composed of 45 anonymised image pairs (90 single images) was graded by 20 task force members in two rounds separated by 10 days. The intra-reader (mean: 0.79; 95% confidence interval: 0.75-0.84) reliability was excellent and the inter-reader (mean: 0.75; 95% confidence interval: 0.74-0.76) reliability was substantial. <h3>Conclusion</h3> This preliminary OMERACT scoring system for bone erosions of the finger joints in RA has demonstrated excellent reliability on static images. Further studies are required to evaluate the reliability of the combined acquisition and reading of images in patients. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0086 A TRANSVERSAL STUDY OF 826 UNTREATED GOUT PATIENTS SHOWS THAT ECHOGENICITY OF THE RENAL MEDULLA INCREASES WITH GOUT DURATION/SEVERITY AND STEROID USE
Authors: T. Bardin, Q. Nguyen, K. Tran, C. Tran, D. Huynh, D. M. Do, P. Richette, J. M. Correas, M. Resche-Rigon
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Diffuse hyperechogenicity of the kidney pyramids, detected by kidney ultrasound (US) scan, has been reported as a frequent finding in severe, untreated, tophaceous gout. It seemed related to crystal deposition in the renal medulla and correlated with kidney function decrease, reviving the concept of gouty microcrystalline nephropathy [1]. <h3>Objectives</h3> To confirm this finding and to detect its progression with gout duration. <h3>Methods</h3> Patients fulfilled the ACR/EULAR criteria, were not treated by urate-lowering drugs (ULD) at the time of examination; 44 % had received short courses of ULD in the past. They underwent kidney US scans by an experienced radiologist, who classified each kidney into 3 grades according to the presence and degree of hyperechogenicity of the renal pyramids, as compared to the renal cortex. Grade 0 was defined as no medulla hyperechogenicity; grade 1 by the observation of hyperechogenic spots in 1 or 2 renal pyramids; grade 3 as a diffuse hyperechogenicity of at least 3 pyramids (out of 5 scanned). Demographic variables, comorbidities, gout and biochemical features were retrieved from electronic files. US scans of the MTP joints allowed gradation of double contours from 0 to 3. Links between patients 'features and renal medulla staging were assessed by Fisher exact or Kruskall and Wallis tests according to the type of variables. Multivariable analysis included all statistically significant features, with model selection on p.value using a proportional odds logistic regression model. All test were two-sided. <h3>Results</h3> 826 consecutive new patients were included from August 1 to December 24, 2022. 88 % were males, median age was 49 years, median BMI 24.22 kg/m<sup>2</sup>, median gout duration 5 years, 70 % of patients had clinical tophi, median uricemia was 488,6 µmol/l, median creatininemia 83.5 mmol/l, median eGFR 93 ml/min. Both kidneys were classified at the same grade in every all patients. 65.5% of patients were at grade 0, 17.8 % at grade 1 and 16.7 % at grade 3. Table 1 shows links of the extent of medulla hyperechogenicity with patients 'features. By multivariable analysis, positive correlation was found with male sex, hypertension, gout duration, tophi, double contours and uricemia; BMI, eGFR and cortilsolemia negatively correlated. <h3>Conclusion</h3> Hyperechogenicity of the renal medullas progressively increased with gout duration, MSU deposition and steroid treatment, and associated with decrease of renal function and hypertension. These observations reinforce the early indication of ULDs in gouty patients. <h3>Reference</h3> [1]Bardin T et al. Kidney Intern 2021;99: 218–226 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0272 IMPACT OF THE COVID-19 PANDEMIC ON ADHERENCE TO DISEASE MODIFYING DRUGS AMONG PATIENTS WITH RHEUMATIC DISEASES: A POPULATION-BASED, INTERRUPTED TIME SERIES ANALYSIS
Authors: N. Rebić, E. C. Sayre, M. Law, M. De Vera
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Although studies have quantified adherence to medications among patients with rheumatic diseases (RD) during the COVID-19, lack of direct pre-pandemic comparison precludes understanding of impact of the pandemic. <h3>Objectives</h3> Our objective was to evaluate the effect of the COVID-19 pandemic on adherence to disease modifying drugs (DMARDs) including conventional synthetic (csDMARDs) and targeted synthetic (tsDMARDs). <h3>Methods</h3> We linked population-based health data on all physician visits, hospital admissions, and all dispensed medications, regardless of payer in British Columbia from 01/01/1996 to 3/31/2021. We identified prescriptions for csDMARDs (including methotrexate, hydroxychloroquine) and tsDMARDs, namely anti-TNFs (including infliximab, etanercept, adalimumab) and rituximab using drug identification numbers among indicated individuals with RD. We defined March 11, 2020, as the 'index date' which corresponded to the date that mitigation measures for the COVID-19 pandemic were first introduced. We assessed adherence as proportion days covered (PDC), calculated monthly in the 12 months before and 12 months after the index date. We used interrupted time-series models, namely segmented regression to estimate changes and trends in adherence before and after the index date. <h3>Results</h3> Our analysis showed that the mean PDCs for all included DMARDs stayed relatively steady in the 12 months before and after mitigation measures were introduced (see <b>Table 1</b>). Adherence was highest among anti-TNFs, methotrexate, and azathioprine. Anti-TNFs were on a downward trajectory 12 months prior to the index date. Interrupted time-series modeling demonstrated statistically significant differences in the trends in PDCs post- vs. pre-mitigation measures for all anti-TNFS (slope [∂]: 1.38, standard error [SE]: 0.23), infliximab (∂: 1.35, SE: 0.23), adalimumab (∂: 0.82, SE: 0.25), and etanercept (∂: 1.07, SE: 0.25) (see <b>Figure 1a</b>). Conversely, the csDMARDs were on a flatter trajectory, and methotrexate (∂: -0.53, SE: 0.16), leflunomide (∂: 0.43, SE: 0.08), mycophenolate (∂: -1.26, SE: 0.48), cyclophosphamide (∂: 0.29, SE: 0.05), minocycline (∂: 0.04, SE: 0.02), chloroquine (∂: 0.02, SE: 0.00) showed statistically significant changes in estimated PDC trajectory after mitigation measures were introduced (see <b>Figure 1b</b>). <h3>Conclusion</h3> This population-based study demonstrates that messaging and pandemic mitigation measures did not affect adherence to DMARDs. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0046 AUTOINFLAMMATORY GENETIC VARIANTS ARE OVER-REPRESENTED IN ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS COMPARED TO RHEUMATOID ARTHRITIS AND PSORIASIS
Authors: Q. LI, A. Dohey, D. Codner, P. Rahman
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ankylosing Spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory diseases of undetermined etiology. Both entities exhibit features of autoimmunity (exhibited by clonal expansion of T cell populations) and autoinflammation, as noted by the aberrant activity of innate and innate-like cells [1]. <h3>Objectives</h3> In this study, we screen for genetic variants associated with known autoinflammatory disease in patients with AS, PsA, and compare it to rheumatoid arthritis (RA) and psoriasis (Ps). <h3>Methods</h3> The UK genome biobank identified exomes of AS, PsA, RA, and Ps patients. Autoinflammatory genes were selected from the blueprint autoinflammatory syndrome panel [2]. Twenty thousand nine hundred five missense mutations were identified from the 47 autoinflammatory genes in the blueprint panel and screened in these four cohorts. Mutational burden, mutation number, and mutation rate in these 47 genes were calculated. <h3>Results</h3> Exonic mutations of 1264 in AS, 886 in PsA, 5361 in RA and 5567 in Ps patients from the UK biobank were enrolled and analyzed in this study. The number of autoinflammatory variants identified was 937 in AS, 780 in PsA, 2081 in RA and 2015 in Ps. The average mutation rate in 47 genes is around 0.26 for these four diseases. The autoinflammatory panel's average mutation burden was not significantly different between these diseases (116 in AS and PsA, 118 in RA and Ps). However, when we accounted for the number of individuals screened, AS and PsA had a higher mean number of autoinflammatory variants than RA and Ps. Specifically, AS and PsA patients had a mean number of 0.741 and 0.880 variants per individual, respectively, compared to 0.388 and 0.362 for RA and Ps, respectively. <h3>Conclusion</h3> This study strengths the role of autoinflammation in AS and PsA as we report an overabundance of autoinflammatory variants in AS and PsA compared to RA and psoriasis. Consideration of autoinflammatory etiology may impact current diagnostic and therapeutic approaches. <h3>References</h3> [1]Mauro D, Thomas R, Guggino G, Lories R, Brown MA, Ciccia F. Ankylosing spondylitis: an autoimmune or autoinflammatory disease? Nat Rev Rheumatol. 2021 Jul;17(7):387-404. doi: 10.1038/s41584-021-00625-y. Epub 2021 Jun 10. PMID: 34113018. [2]https://blueprintgenetics.com/tests/panels/immunology/autoinflammatory-syndrome-panel/ <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Quan Li: None declared, Amanda Dohey: None declared, Dianne Codner: None declared, Proton Rahman Speakers bureau: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, Consultant of: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis.
POS0170 ALL-CAUSE MORTALITY AND THE INCIDENCE OF CANCER IN PATIENTS WITH MODERATE-TO-SEVERE SLE: RESULTS FROM THE BRITISH ISLES LUPUS ASSESSMENT GROUP BIOLOGICS REGISTRY (BILAG-BR)
Authors: M. Rodziewicz, S. Dyball, E. Sutton, S. Mcdonald, B. Parker, I. N. Bruce
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Patients with systemic lupus erythematosus (SLE) are known to have an increased mortality and risk of certain cancers compared to the general population. <h3>Objectives</h3> We aimed to characterise the all-cause mortality rate (MR) and the incidence of cancer in SLE patients receiving biologic and standard of care (SoC) therapies. <h3>Methods</h3> Patients recruited to the BILAG-BR 2010-2021 were included. Demographic and clinical data were recorded at recruitment. Mortality and malignancy data were collected from study centres, the UK Office of National Statistics and the National Cancer Register. Cox regression models were used to estimate the hazard ratios (HRs) of mortality and cancer in biologic-treated patients compared to SoC. Mortality models were adjusted for age, gender, co-morbidity, SLICC damage index (SDI) and hydroxychloroquine (HCQ) use. The standardised mortality ratio (SMR) and standardised incidence ratio (SIR) were calculated using death and cancer rates for the general UK population. <h3>Results</h3> During follow-up, (1463 patients with 5,962 person years [pys]), 32 incident cancers occurred in 31 individuals, a median (IQR) of 1.31 (0.63-3.36) years after registration. The overall incidence was 6.0 (3.8-7.6) per 1000 pys. Compared to the UK general population, the SIR (95% CI) was 1.21 (0.85-1.72). Using SoC as the comparator, the age and gender adjusted HR was 1.49 (0.57-3.92) for rituximab and 2.47 (0.57-10.58) for belimumab. Across the whole cohort, associated risk factors (table 1), included age at recruitment (HR 1.05 [1.02-1.08]) and male sex (HR 2.68 [1.13-6.41]). Following registration, 54 deaths occurred after a median of 1.8 (0.8-3.3) years. Crude MR was 9.15 (7.0-11.9) per 1000 pys. The SMR was 4.74 (3.63-6.19). The most common causes of death were infection (22, 40.7%), SLE (11, 20.3%) and cancer (6, 11.1%). MR was 3.3 (1.3-8.9) per 1000 py in the SoC, 11.3 (8.5-15.0) in the rituximab and 2.5 (0.4-17.9) in the belimumab group. Risk factors included age at recruitment (HR 1.07 [1.05-1.09]) and SDI (HR 1.34 [1.08-1.67]. HCQ use was protective (HR 0.30 [0.14-0.65]). In multivariate analysis, compared to SoC, risk was similar in rituximab (HR 2.36 [0.69-8.10) and belimumab groups (HR 1.41 [0.14-14.14]). <h3>Conclusion</h3> Although overall numbers are low, mortality rate and incidence of cancer appears to be broadly similar in SoC, rituximab and belimumab treated patients. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Mia Rodziewicz: None declared, Sarah Dyball: None declared, Emily Sutton: None declared, Stephen McDonald: None declared, Ben Parker: None declared, Ian N. Bruce Speakers bureau: GSK Astra Zeneca Janssen , Consultant of: GSK Astra Zeneca Aurinia Lilly , Grant/research support from: GSK Astra Zeneca Janssen.
POS0355 CLINICAL TRAIT-SPECIFIC GENETIC ANALYSIS IN BEHÇET’S DISEASE IDENTIFIES NOVEL LOCI ASSOCIATED WITH OCULAR AND NEUROLOGICAL INVOLVEMENT
Authors: D. Casares-Marfil, D. Esencan, F. Alibaz-Oner, A. Cefle, A. Yazici, N. Duzgun, M. A. Aşik, S. Özbek, M. Çinar, E. Alpsoy, N. S. Yasar Bilge, T. Kaşifoğlu, G. Saruhan-Direskeneli, H. Direskeneli, A. H. Sawalha
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. <h3>Objectives</h3> The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease in a group of patients with &gt; 5 years of follow up. <h3>Methods</h3> A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. <h3>Results</h3> Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and <i>HLA-B</i>/<i>MICA</i> (rs116799036: OR=1.85, 95% CI=1.35-2.52, p-value=1.1x10<sup>-4</sup>). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared with those without ocular involvement, and is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with <i>SLCO4A</i> (rs6062789: OR=0.41 (95% CI=0.30-0.58), p-value=1.92x10<sup>-7</sup>), and neurological involvement with <i>DDX60L</i> (rs62334264: OR= 4.12 (95% CI 2.34 to 7.24), p-value = 8.85x10<sup>-7</sup>). <h3>Conclusion</h3> Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations. <h3>References</h3> None. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.